1. Field of the Invention
The present invention generally relates to the fields of organ transplantation and reconstructive surgery, and to the new field of tissue engineering. More specifically, the present invention defines a new method and materials for providing a compact microfluidic system capable of filtering impurities and waste products from the blood stream to treat patients suffering from damaged, malfunctioning or failing vital organs, such as the kidney and liver.
2. Description of the Related Art
There are two principal therapeutic avenues for patients suffering from diseased, malfunctioning or failing vital organs responsible for blood filtration. One of these avenues involves organ assistance devices, such as the use of hemodialysis circuits in the renal unit of hospitals, or bridge therapy for liver failure such as the ELAD (Liver Assist Device). In the case of kidney dialysis, patients typically undergo 3 4-hour hemodialysis treatments per week in the clinic, each involving a trip to the clinic and a process in which the patient is connected to a large piece of equipment which filters waste products such as urea and creatinine from the blood stream while maintaining electrolyte, glucose and protein balances.
These treatments, while effective at sustaining life for ESRD (End-Stage Renal Disease) patients, are highly invasive, and are limited in effectiveness due to the non-physiological concentration profile of waste and impurities in the bloodstream. Namely, the concentration of urea, for example, becomes elevated well beyond levels in healthy patients for the 2-3 days between treatments, and is then lowered very rapidly during dialysis. These drastic excursions in concentration lead to complications and distress in dialysis patients, and the psychological impact of dialysis is associated with a sharp increase in suicide rates among the patient population. Most significantly, the long-term prognosis for ESRD patients on dialysis is poor, with 5-year survival rates of less than 20%.
The cost of these treatments is staggering, totaling approximately $12 Billion per year for the roughly 300,000 ESRD patients, or $40,000 per year per patient. For patients with liver failure, liver assist devices provide only bridge therapy, perhaps a few weeks at best, until a replacement liver is available.
The second avenue of treatment for patients with failing organs such as liver and kidney is transplantation, in which a donor organ is implanted into the patient from a variety of sources. These sources include cadaveric organs, which are in extremely limited supply, and therefore the number of patients on the waiting list for a vital organ is approaching 100,000 in the United States. Organ rejection by the recipient's immune system represents a huge challenge for the field of transplant medicine, because it severely limits the potential donor pool. Even when the donor is a match, recipients are consigned to a lifetime of immunosuppressive drugs, which are extremely expensive and are associated with a host of severe side effects. Other sources for donor tissue and organs are living donor transplants, which in the case of the kidney involve one organ from a donor with two healthy kidneys, or split liver transplants in which part of the liver of a healthy patient is transplanted into the recipient. Often involving family members, these transplants are typically safe for the donor but have led to well-documented cases in which previously healthy donors suffered lethal complications following transplant surgery.
Avenues beyond these two involve experimental procedures not yet ready for wide clinical practice. These include the use of artificial mechanical organs, such as the artificial fully implantable heart, biohybrid organs involving combinations of mechanical/artificial materials and devices and living cells and tissues, and fully natural tissue engineered organs which replace function.
The principal disadvantages of the two general approaches described above relate to the insufficient replacement of physiological organ function without serious limitations or complications. In the case of renal assist devices, specifically, the invasive, complex and discontinuous nature of the treatments limit their therapeutic value, because they do not provide patients with benefits concomitant with a healthy pair of kidneys. These disadvantages can be understood as being associated with limitations in the technology which insufficiently reproduce organ function, and limitations associated with cost, complexity and accessibility. The former set of challenges can be addressed by advances in dialysis involving either acellular processes (superior filtration, hemocompatibility, etc.) or cell-based processes (improvements in the resorption circuit which returns desired blood components to the body following ultrafiltration). The latter set of challenges relates to the fact that dialysis treatments are costly and labor-intensive, require frequent visits to the clinic and large, complex machines, and are not continuous because of the need for centralized dialysis clinics often distant from their patients.
Compact organ assist devices with continuous filtration that is physiologic in nature would provide enormous patient benefit. Moreover, a wearable, continuous device will reduce costs and labor associated with treatment, and will eliminate most visits to the clinic except for maintenance and monitoring. Accordingly, there is a need for improved systems.